Method of preparing crosslinked biomaterial compositions for use in tissue augmentation

• US 5,550,187 A
• Filed: 08/08/1994
• Issued: 08/27/1996
• Est. Priority Date: 11/21/1988
• Status: Expired due to Term

• Current Assignee: Angiotech Pharmaceuticals Incorporated
• Original Assignee: Collagen Corp. (Abbvie Incorporated)
• Inventors: Rhee, Woonza M., Berg, Richard A., Smestad, Thomas L., Rosenblatt, Joel S., Braga, Larry J., Tefft, Jacqueline A.
• Primary Examiner(s): Nutter, Nathan M.
• Application Number:
  US08/287,549
• Time in Patent Office: 750 Days
• Field of Search: 525/54.1, 523/113, 424/423
• US Class Current: 525/54.1
• CPC Class Codes: A61F 2/07 Stent-grafts
• CPC Class Codes: A61F 2310/00365 Proteins; Polypeptides; Degradation products thereof
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61L 15/225 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 24/08 Polysaccharides A61L24/043 takes precedence
• CPC Class Codes: A61L 24/102 Collagen
• CPC Class Codes: A61L 2430/16 for reconstruction of eye parts, e.g. intraocular lens, cornea
• CPC Class Codes: A61L 26/0033 Collagen
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/20 Polysaccharides
• CPC Class Codes: A61L 27/24 Collagen
• CPC Class Codes: A61L 27/26 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/44 having a macromolecular matrix
• CPC Class Codes: A61L 31/041 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 31/042 Polysaccharides
• CPC Class Codes: A61L 31/044 Collagen
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/125 having a macromolecular matrix
• CPC Class Codes: C08H 1/06 derived from horn, hoofs, hair, skin or leather
• CPC Class Codes: C08L 2666/02 : Organic macromolecular compounds, natural resins, waxes or and bituminous materials
• CPC Class Codes: C08L 5/00 : Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
• CPC Class Codes: C08L 71/02 : Polyalkylene oxides
• CPC Class Codes: C08L 89/00 : Compositions of proteins; Compositions of derivatives thereof foodstuff preparations A23J3/00
• CPC Class Codes: C08L 89/06 : derived from leather or skin , e.g. gelatin
• CPC Class Codes: C09J 189/06 : derived from leather or skin
• CPC Class Codes: G02B 1/043 : Contact lenses

Abstract

The present invention discloses a novel method for preparing crosslinked biomaterial compositions for use in the augmentation of soft or hard tissue. In general, the method comprises mixing a biocompatible polymer, which is preferably collagen, with a sterile, dry crosslinking agent, which is preferably a synthetic hydrophilic polymer such as a functionally activated polyethylene glycol. Also provided are preferred processes for preparing sterile, dry crosslinking agents contained within syringes for use in the method of the invention. Methods for sterilization of the crosslinking agent include, but are not limited to, sterile filtration, aseptic processing, and e-beam or gamma irradiation. Methods for providing augmentation of soft or hard tissue using crosslinked biomaterial compositions prepared according to the method of the invention are also disclosed.

Claims

1. A method of preparing a formed implant comprising a crosslinked biomaterial composition comprising the steps of:

providing a device for extruding a biocompatible polymer and a device for extruding a sterile, dry crosslinking agent;

mixing the biocompatible polymer and the crosslinking agent to initiate crosslinking between the biocompatible polymer and the crosslinking agent;

extruding the biocompatible polymer and the crosslinking agent into a mold having a desired size and shape; and

allowing the biocompatible polymer and the crosslinking agent to crosslink within the mold to produce a formed implant having a desired size and shape.

2. The method of claim 1, wherein the biocompatible polymer is selected from the group consisting of collagen, a collagen derivative, a glycosaminoglycan, a glycosaminoglycan derivative, and mixtures thereof.

3. The method of claim 2, wherein the collagen is atelopeptide fibrillar collagen.

4. The method of claim 2, wherein the glycosaminoglycan is selected from the group consisting of:

hyaluronic acid, chondroitin sulfate A, chondroitin sulfate C, dermatan sulfate, keratan sulfate, keratosulfate, chitin, chitosan, heparin, and mixtures thereof.

5. The method of claim 1, wherein the crosslinking agent is a synthetic hydrophilic polymer containing a functional group capable of forming a covalent bond with a primary amino group on a biocompatible polymer molecule.

6. The method of claim 5, wherein synthetic hydrophilic polymer is a polyethylene glycol that has been chemically derivatized to contain a functional group capable of forming a covalent bond with a primary amino group on a biocompatible polymer molecule.

7. The method of claim 6, wherein the polyethylene glycol has been chemically derivatized to contain two functional groups capable of forming covalent bonds with primary amino groups on biocompatible polymer molecules.

8. A method of providing a coating comprising a crosslinked biomaterial composition on a surface of a synthetic implant comprising the steps of:

providing a device for extruding a biocompatible polymer and a device for extruding a sterile, dry crosslinking agent;

mixing the biocompatible polymer and the crosslinking agent to initiate crosslinking between the biocompatible polymer and the crosslinking agent;

extruding the biocompatible polymer and the crosslinking agent onto a surface of a synthetic implant; and

allowing the biocompatible polymer and the crosslinking agent to crosslink on the surface of the synthetic implant to provide a crosslinked biomaterial coating on the surface of the implant.

9. The method of claim 8, wherein the biocompatible polymer is selected from the group consisting of collagen, a collagen derivative, a glycosaminoglycan, a glycosaminoglycan derivative, and mixtures thereof.

10. The method of claim 9, wherein the collagen is atelopeptide fibrillar collagen.

11. The method of claim 9, wherein the glycosaminoglycan is selected from the group consisting of:

hyaluronic acid, chondroitin sulfate A, chondroitin sulfate C, dermatan sulfate, keratan sulfate, keratosulfate, chitin, chitosan, heparin, and mixtures thereof.

12. The method of claim 8, wherein the crosslinking agent is a synthetic hydrophilic polymer containing a functional group capable of forming a covalent bond with a primary amino group on a biocompatible polymer molecule.

13. The method of claim 12, wherein the synthetic hydrophilic polymer is a polyethylene glycol that has been chemically derivatized to contain a functional group capable of forming a covalent bond with a primary amino group on a biocompatible polymer molecule.

14. The method of claim 13, wherein the polyethylene glycol has been chemically derivatized to contain two functional groups capable of forming covalent bonds with primary amino groups on biocompatible polymer molecules.